Reaction-diffusion model of Rho-GTPase signaling quantitatively reproduces different types of complex actin dynamics.

Abstract

In this work, we developed a computational model of Rho-GTPase activity and applied it to investigate actin wave dynamics in cell cortex. Here we focused on cell-level dynamics of cortical actin in oocytes of two organisms: Patiria miniata (starfish) and Xenopus laevis (frog). The model showed a defining role of the early low-activity phase of pattern formation in the development of long-term, high-activity wave dynamics. To our best knowledge, such low-activity dynamics was not described before, however different paths of its destabilization explain GTPase activity at the later experimentally observable phase. In starfish, this complex transient behavior leads to the formation of multiple distinct regions of coherent activity (that we termed ‘wave domains’). In frog, spatiotemporal dynamics is different and does not exhibit wave domains. By accounting for the intrinsic noise, our model quantitatively reproduced experimentally observed dynamics in both starfish and frog. We determined parameters responsible for the transition from starfish to frog phenotype, which shed light on the difference in the regulatory pathways of the two organisms. For our quantitative analysis, we developed a novel approach to identification and characterization of wave domains allowing for direct comparison of simulated and experimental images. Overall, our findings provide an insight into the organization of the Rho signaling motif responsible for very complex but still computationally reproducible cell-level actin dynamics.